LncRNAs, nuclear architecture and the immune response

Abstract

Long noncoding RNAs (LncRNAs) are key regulators of gene expression and can mediate their effects in both the nucleus and cytoplasm. Some of the best-characterized lncRNAs are localized within the nucleus, where they modulate the nuclear architecture and influence gene expression. In this review, we discuss the role of lncRNAs in nuclear architecture in the context of their gene regulatory functions in innate immunity. Here, we discuss various approaches to functionally characterize nuclear-localized lncRNAs and the challenges faced in the field.

Keywords: Chromatin; innate immunity; long noncoding RNAs; macrophages; nucleus.

Figure 1.

Mechanisms of immune gene regulation by nuclear-localized lncRNAs. a, female-specific X-inactive specific transcript (XIST) is a rich source of TLR7 ligands and consequent activation. XIST harbors a GUCCUUAA motif that induces TLR7. This proinflammatory role of XIST is found to be most common in women with systemic lupus erythematous (SLE), possibly explaining why women are more likely to be affected by SLE. b, Nuclear enriched abundant transcript 1 (NEAT1) is essential to forming paraspeckles in the nucleus and inducing antiviral cytokine production upon viral infection. NEAT1 transcription is increasingly induced upon viral infection, producing excess paraspeckle formation in the nucleus and inducing IL8 production. c, 3D chromatin looping allows lncRNAs to regulate immune genes in cis. Upstream master lncRNA of the inflammatory chemokine locus (UMLILO) directs transcription factors across chemokine promoters, enabling epigenetic priming for their transcription. LincRNA-Cox2 is a multifunctional locus that can regulate Ptgs2 through an enhancer mechanism.